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Biomedical subjects

J L Excler

Publications and source records attributed to J L Excler.

At least 37 records · Page 2Linked to original sources

A prime-boost approach to HIV preventive vaccine using a recombinant canarypox virus expressing glycoprotein 160 (MN) followed by a recombinant glycoprotein 160 (MN/LAI). The AGIS Group, and l'Agence Nationale de Recherche sur le SIDA.

The safety and the immunogenicity of a recombinant canarypox live vector expressing the human immunodeficiency virus type 1 (HIV-1) gp160 gene from the MN isolate, ALVAC-HIV (vCP125), followed by booster injections of a soluble recombinant hybrid envelope glycoprotein MN/LAI (rgp160), were evaluated in vaccinia-immune, healthy adults at low risk for acquiring HIV-1 infection. Volunteers (n = 20) received vCP125 (10(6) TCID50) at 0 and 1 month, followed randomly by rgp160 formulated in alum or in Freund's incomplete adjuvant (FIA) at 3 and 6 months. Local and systemic reactions were mild or moderate and resolved within the first 72 hr after immunization. No significant biological changes in routine tests were observed in any volunteer. Two injections of vCP125 did not elicit antibodies. Neutralizing antibodies (NA) against the HIV-1 MN isolate were detected in 65 and 90% of the subjects after the first and the second rgp 160 booster injections, respectively. Six months after the last boost, only 55% were still positive. Seven of 14 sera with the highest NA titers against MN weakly cross-neutralized the HIV-1 SF2 isolate; none had NA against the HIV-1 LAI or against a North American primary isolate. Specific lymphocyte T cell proliferation to rgp 160 was detected in 25% of the subjects after vCP125 and in all subjects after the first booster injection and 12 months after the first injection. An envelope-specific cytotoxic lymphocyte activity was found in 39% of the volunteers and characterized for some of them as CD3+, CD8+, MHC class I restricted. The adjuvant formulation did not influence significantly the immune responses.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS Vaccines↗

A 3-week hepatitis B vaccination schedule provides rapid and persistent protective immunity: a multicenter, randomized trial comparing accelerated and classic vaccination schedules.

Hepatitis B (HB) vaccinations given once weekly for 3 weeks can provide early seroprotection. This study compared immune responses induced by the accelerated (A; days 0, 10, 21) and classic (C; days 0, 28, 56) HB vaccination schedules. Two hundred seventy healthy subjects (95 men, 175 women) with a mean age of 23.8 years received 3 doses of GenHevac B, a recombinant vaccine produced in mammalian cells. The subjects were randomly assigned to schedules A or C. A booster dose was given 1 year later. One month after the third dose, 70% (schedule A) and 92% (schedule C) of the subjects were seroprotected and 100% (A) and 99% (C) had developed anti-pre-S2 antibodies. Before booster injections, 93% (A) and 95% (C) of the subjects were seroprotected, and 1 month after the booster, almost all subjects were seroprotected. A 3-week HB vaccination schedule with GenHevac B can confer early protective immunity lasting up to 1 year.

Adolescent↗

Avoiding missed opportunities for immunization in the Central African Republic: potential impact on vaccination coverage.

Quantified in the study are the extent of missed opportunities for immunization and the potential increases in vaccination coverage and timeliness that could be achieved by using all health centre visits to administer childhood vaccinations in the Central African Republic. The data were collected during a national vaccination coverage survey of 642 children aged 12-23 months from three areas: rural, urban, and the capital, Bangui. Dates of all vaccination visits and other health centre visits were obtained from combined vaccination/health cards. Nationwide, 70% of all opportunities for valid measles vaccination were missed. Of these, 28% occurred at visits when at least one vaccine was given, while 72% occurred at other health centre visits. If there had been no missed opportunities to administer all vaccinations due when at least one vaccine was given, the coverage would have increased from 53% to 67% for the diphtheria-pertussis-tetanus series, from 54% to 70% for measles, and from 34% to 59% for all antigens. If there had been no missed opportunities at any visit, the corresponding increases would have been to 70%, 76%, and 65%. For measles, 46% of the potential increase depends on recognizing that an earlier dose of the vaccine was invalid and on revaccinating. Days-at-risk for measles (after the age of 270 days) would have been reduced by a mean of 74 days per subject with a health card had no opportunities been missed. The method used serves as a valuable adjunct to evaluations of missed opportunities based on exit interviews at health facilities.(ABSTRACT TRUNCATED AT 250 WORDS)

Central African Republic↗

The safety and use of canarypox vectored vaccines.

ALVAC recombinants have been administered to humans and animals by parenteral and oral routes without giving signs of replication, systemic dissemination or severe reaction. In principle, it should be impossible for canarypox recombinants to disseminate in the environment as they would not be synthesised in mammalian cells as complete virus. Canarypox vectors have been safe for humans, in whom there has been no evidence of replication, but more work needs to be done to prove absence of replication. Recombinants are immunogenic by the intramuscular and subcutaneous routes. They are also immunogenic when given orally, but the dose required is still under study. Canarypox recombinants effectively prime the immune system for induction of antibodies and CD8 cell-mediated cytotoxicity by protein antigens. Antibody responses are not influenced by prior inoculation of canarypox, of subunit vaccine corresponding to the gene insert, or of vaccinia. Canarypox virus is attenuated for canaries, in which species it is already widely used. In principle, it is non-infectious for humans or other mammals. It may be infectious for other birds.

AIDS Vaccines↗

[Recombinant vaccine and extracting vaccine against hepatitis B in patients with kidney insufficiency: comparative immunogenicity].

OBJECTIVES: Patients with chronic renal failure respond rather poorly to hepatitis B vaccines. A better response could be expected from recombinant vaccines including both the S and the pre-S2 antigens. We therefore prospectively compared the immunogenicity of plasma-derived Hevac B vaccine (H) with that of recombinant GenHevac B vaccine (G). METHODS: Vaccinations were performed in 120 non-dialyzed patients with chronic renal failure. The patients were randomly divided into two groups. Group G included 60 patients (24 males, mean age 58 +/- 16 years, mean creatinine clearance 25.3 +/- 12.6 ml/min) who were given the Hevac B vaccine at the dose of 5 micrograms. Group H included 60 patients (31 males, mean age 60 +/- 15 years, mean creatinine clearance 24.4 +/- 11.1 ml/min) who were given GenHevac B vaccine at the dose of 20 micrograms. All vaccinations were repeated at 0, 1, 2, 4 and 12 months. RESULTS: Following the fourth injection, seroconversion (anti-Hbs > or = 2 mlU/ml) was observed in 50/59 (85%) of the patients in group G versus 38/58 (67%) in group H (p < 0.02). Seroprotection (> or = 10 mlU/ml) was obtained in 42/59 (71%) vs 34/58 (59%), (NS) in the two groups respectively with a geometric mean titer of 112 versus 229 mlU/ml (NS) in responders. Following the booster injection at the 12th month, seroconversion was achieved in 48/51 (94%) vs 40/53 (76%) (p < 0.01) and seroprotection in 84% vs 70% (p = 0.053) respectively. The mean geometric titers were 879 and 1001 mlU/ml. CONCLUSIONS: Recombinant GenHevac B vaccine elicits seroconversion and seroprotection in a higher proportion of patients with chronic renal failure than the plasma-derived Hevac B vaccine, with comparably high antibody titers in responders. Therefore, GenHevac B vaccine should be recommended for vaccinating patients with chronic renal failure against hepatitis B.

Adult↗

A 5-year immunization field trial against hepatitis B using a Chinese hamster ovary cell recombinant vaccine in French Polynesian newborns: results at 3 years.

A hepatitis immunization field trial, using a Chinese hamster ovary (CHO) cell recombinant vaccine, was implemented for newborns in the Austral archipelago of French Polynesia in 1988. Three different schedules were used: (1) four vaccine doses at months (M) M0, M1, M2 and M12; (2) three vaccine doses at M0, M1 and M6; and (3) three vaccine doses at M0, M1 and M12. The programme evaluation was performed yearly at fixed dates, i.e. October-November 1989, 1990 and 1991. After the third year, of the 582 children who received one or more doses of vaccine, four were HBsAg carriers. After one or two doses, 88 and 98%, respectively, had seroconverted for at least one of the two measured antibodies, anti-HBs or anti pre-S2. After three doses, seroconversion rates and geometric mean anti-HBs titres were, respectively, 94% and 187 mIU ml-1 using schedule M0, M1, M2; 95% and 507 mIU ml-1 using schedule M0, M1, M6 and 96% and 476 mIU ml-1 using schedule M0, M1, M12. After four doses (M0, M1, M2, M12) the corresponding results were 99% and 1518 mIU ml-1. One of the 16 vaccinated neonates born to HBsAg/HBeAg-positive mothers was an HBsAg carrier, implying a protective rate for the prevention of perinatal transmission of 93%. Overall, these results indicate that, in field conditions, indiscriminate vaccination of newborns with a CHO-recombinant vaccine without hepatitis B immunoglobulin (HiBG) resulted in high immunogenicity. Final evaluation in 1993-1994 will permit confirmation of the effectiveness of the two three-dose vaccine schedules.

Animals↗

Immunogenicity of the recombinant GenHevac B Pasteur vaccine against hepatitis B in chronic uremic patients.

Immunogenicity of the recombinant GenHevac B vaccine (G), containing both the S and the preS2 antigen, was compared with that of the plasma-derived Hevac B (H) vaccine in 120 chronic uremic predialysis patients. Sixty received 20 micrograms/dose of G and 60 received 5 micrograms/dose of H at 0, 1, 2, 4, and 12 months. Two months after the fourth injection, seroconversion (antibody to hepatitis B surface antigen [HBs], > or = 2 mIU/mL) was seen in 85% of group G and 67% of group H patients (P < .02); seroprotection (anti-HBs, > or = 10 mIU/mL) was seen in 71% and 59%, respectively. The geometric mean titers (GMT) of anti-HBs in responders were 112 and 229 mIU/mL, respectively. After booster injection at month 12, seroconversion occurred in 94% and 76% and seroprotection in 84% and 70%, with anti-HBs GMTs of 879 and 1001 mIU/mL in groups G and H, respectively. The recombinant GenHevac B vaccine elicited seroconversion and seroprotection in a higher proportion of chronic uremic patients, with comparably high anti-HBs antibody titers in responders.

Adult↗

Three-week hepatitis B vaccination provides protective immunity.

To determine whether a 3-week hepatitis B (HB) vaccination could achieve protective immunity, 89 healthy non-immunized young adults received three doses of 20 micrograms each of HBs antigen (GenHevac B, Pasteur) and were randomly assigned to schedule A (n = 44): two doses at day 0, one dose at day 21; or schedule B (n = 45): one dose at days 0, 10 and 21. Seroprotection rates (anti-HBs > or = 10 mIU ml-1) for groups A and B respectively were: 23 and 40% at day 21; and 77 and 91% at day 82 (not significant). Anti-HBs geometric mean titres were higher in group B than in group A (p < 0.05) at days 21 (6.4 versus 3.8) and 82 (77.6 versus 33.5). One year after primary vaccination, the seroprotection rate remained as high as 90% in the vaccinees of group B; after boosting all vaccinees had protective levels of anti-HBs antibodies. Thus 3-week HB vaccination with GenHevac B allowed early and durable protective immunity.

Adolescent↗

Sero-epidemiological survey for toxoplasmosis in Burundi.

The first sero-epidemiological survey for toxoplasmosis in Burundi was conducted in 1985. The global prevalence among 622 subjects tested in ELISA and IFI was 44.1% with a higher rate in men (49.6%) than in women (39.2%, p less than 0.01). The highest prevalences were observed in rural areas with intensive farming activities: the crest (57.9%), the plain (53.3%). The central platform, where people and farming activities are widespread, had a lower prevalence (29.3%, p less than 0.001). The risk of infection is much lower in urban people with high levels of hygiene (22.4%) specially in women (13%), than in those of poor condition (45%, p less than 0.001). These data suggest that toxoplasmic infection is mainly due to oocysts ingestion associated with low levels of hygiene and to a lesser extent to meat consumption in men.

Adolescent↗

Assessment of proportional growth of very low birth weight infants fed banked human milk.

Twenty appropriate (mean +/- S.D., gestational age (AGA): 29.9 +/- 1.5 weeks) and 15 small (GA: 34.6 +/- 2.4 weeks) for gestational age (SGA) very low birth weight infants fed banked mature human milk were studied until term for anthropometric parameters: midarm (MAC), chest (CC), head (HC) circumferences, triceps (TSKF) and subscapular (SSKF) skinfold thickness recorded at 15 and 60 s, dynamic skinfold (delta % SKF), muscle (AMA) and fat (AFA) areas, weight and length. In AGA infants, all the parameters at term were significantly lower in extrauterine (EUL) that in intrauterine life (IUL). At term the relative proportion of AFA to total arm area was increased in EUL compared to IUL both in AGA (25.87 +/- 3.8 vs. 23.26 +/- 1.27% respectively, P less than 0.01) and in SGA infants (21.89 +/- 4.63 vs. 18.81 +/- 3.9 respectively, P less than 0.05). SGA infants showed a similar growth in EUL compared to IUL, and a significantly lower AMA and AFA than in AGA infants in EUL. Although HC was in both infants below the 10th centile at term, the ratio weight/HC2 suggests a relative preservation of head growth in EUL compared to IUL (AGA: 20.72 less than 0.87 vs. 22.65 +/- 1.46 respectively, P less than 0.001; SGA; 20.82 +/- 1.16 vs. 21.62 +/- 1.86 respectively, NS). Delta %SKF were negatively correlated with post-conceptional age suggesting a loss of extracellular water in AGA (delta %TSKF: r = -0.287, P less than 0.02) and in SGA infants (delta %TSKF: r = -0.301, P less than 0.02; delta %SSKF: r = -0.316, P less than 0.02). An intrauterine model of discrimination between AGA and SGA infants does not apply to EUL. An equation was established in SGA infants with the best discriminant parameters giving a predictive post-conceptional age: post-conceptual age (PCA) (weeks) = 0.276 HC (cm) + 0.723 CC (cm) - 0.122 MAC (cm) + 0.5 TSKF (mm) + 10.173, (r = 0.867, P less than 0.001) allowing a clear discrimination between AGA and SGA infants. These results suggest that infants show quite different growth patterns between IUL and EUL both for AGA and SGA infants.

Anthropometry↗

[Malnutrition and HIV infection in children in a hospital milieu in Burundi].

HIV infection was present in 18 out of 40 (45%) consecutive malnourished children aged 2 to 29 months in pediatric wards of Bujumbura, Burundi. No difference was observed within and between the seropositive and seronegative groups for sex and anthropometric measures. HIV seropositive cases could be explained by a HIV seropositive mother (83%) or by a transfusion history (17%). The onset of marasmus was earlier in the HIV seropositive group (5 cases observed less than 6 months old compared to none of the other group, Fischer's exact test: P = 0.026). A more complex clinical picture was seen in the HIV seropositive cases (12/18 compared to 4/22, Fischer's exact test: P = 0.004) with the presence of hepatomegaly, adenopathy, thrush, dyspnoea and skin disorders. No difference was observed concerning fever and diarrhoea. HIV seropositive group tended to show a higher hospitalisation frequency and did not well respond to high protein-energy diet: 7 were discharged without gain weight compared to none of the other group (Fischer's exact test: P = 0.011). These results suggest a high rate of vertical transmission mother-child for HIV infection and a frequent association of malnutrition and HIV infection in hospitalized children in Burundi. Marasmic children less than 6 months old should be highly suspected of HIV infection.

Acquired Immunodeficiency Syndrome↗

Anthropometric assessment of nutritional status in newborn infants. Discriminative value of mid arm circumference and of skinfold thickness.

74 appropriate-for-gestational age (AGA) and 22 small-for-gestational age (SGA) caucasian infants were studied for anthropometric parameters: mid arm circumference (MAC), triceps and subscapular skinfold thickness (TSKF and SSKF) recorded at 15 and 60 s, chest circumference (cc), head circumference, birth weight and length. MAC is highly correlated with birth weight either in AGA (r = 0.936; P less than 0.001) or in SGA infants (r = 0.860; P less than 0.001). MAC is also correlated with gestational age in AGA (r = 0.850; P less than 0.001) and SGA infants (r = 0.76; P less than 0.001). Similar correlations were found between TSKF, SSKF and birth weight or gestational age. Arm muscle and fat areas are also positively correlated with birth weight and gestational age, in AGA and SGA infants. A multiple regression analysis of our data allowed a classification of the best discriminant anthropometric parameters between AGA and SGA infants. MAC, SSKF15, SSKF60 and chest circumference were selected. An equation was established in AGA infants with these four parameters giving a predictive gestational age: gestational age (weeks) = 1.216 MAC (cm)-3.588 SSKF15 (mm) + 0.263 CC (cm) + 17.9. The ratio of predicted gestational age to the real gestational age was 1.0 +/- 0.044 in AGA versus 0.896 +/- 0.034 in SGA infants. Our data suggest that MAC and SSKF provide a simple measure of body composition of neonates and a useful tool for determining the degree of maturity of a newborn independent of birth weight.

Anthropometry↗

[Postmeningococcal pericarditis in children. A case favoring an immunoallergic process].

A case of pericarditis following meningococcal meningitis in a 19 month old boy is presented. First clinical signs were noted after 5 days of antibiotherapy (Cefotaxime); at that time the meningitis was cured and the bacteriologic studies yielded negative results. Complete clinical recovery was obtained within 24 hours of treatment with prednisone (2 mg/kg), antibiotherapy being stopped 4 days earlier. The pathogenesis of post meningococcal pericarditis is discussed based on the data from the literature. This observation adds support to an immuno-allergic origin of this pericarditis.

Humans↗

[Infectious hepatitis, acute hemolysis and glucose-6-phosphate dehydrogenase deficiency].

A case of viral hepatitis with hemolytic crisis is an Algerian boy presenting a G-6-P-D deficiency is reported. Hemolysis in G-6-P-D deficient individuals may be precipitated by some viral infection particularly viral hepatitis. During the course of this disease, the destruction of erythrocytes may be explained by an accumulation of metabolites capable of oxidizing hemoglobin SH groups, in the same way as a direct viral perturbation of the red cells glycolytic ways. The two mechanisms do not permit the normal reduction of oxidized hemoglobin. Though, these two diseases are very usual in some countries, this case in uncommon and must be well known.

Acute Disease↗

[Role of maturation in the occurrence of necrotizing enterocolitis].

Over a 3 years and an half period, 40 cases of necrotizing enterocolitis (NEC) are diagnosed in a neonate unit. This represents, 1,22% of total admissions. A new notion is found out: the âge at the onset of NEC is viewed as the post-conceptional age (post-natal age added to gestational age). The cut-off period takes place at 34-36 weeks of post-conceptional age. The low birth weight newborn infants (less than 1 500 g) are significantly more concerned than the others, respectively 5,8% (13/222) and 0,8% (27/3 056). However, the inverse and significant correlation between the delay of onset of NEC and the birth weight is weak. The additional impact of feeding and blood transfusions on the role played by maturation is examined.

Age Factors↗